Smith S A, Richards W E, Caito K, Hanjani P, Markman M, DeGeest K, Gallion H H
Division of Gynecologic Oncology, University of Kentucky, Combs Research Building, Room 124C, 800 Rose Street, Lexington, Kentucky 40536, USA.
Gynecol Oncol. 2001 Dec;83(3):586-92. doi: 10.1006/gyno.2001.6430.
The aims of this study were to determine the frequency of BRCA1 gene alterations in an unselected, clinic-based series of ovarian cancer cases; to evaluate the usefulness of family history in predicting the likelihood of a disease-causing mutation; and to document the occurrence of polymorphic variants in BRCA1 and to determine their distribution among families accordingly to history of breast and/or ovarian cancer.
Two hundred fifty-eight women with primary epithelial ovarian cancer, entered onto a nonclinical protocol of the Gynecologic Oncology Group, were analyzed for BRCA1 germline alterations by single-strand conformation polymorphism analysis.
Protein-truncating mutations in BRCA1 were identified in 12 patients (4.6%). The median age of cancer diagnosis in BRCA1 mutation carriers was 47 years compared to 57 years in patients without mutations (P = 0.02). All but 1 of the patients with BRCA1 mutations reported a family history of breast and/or ovarian cancer and 8 had a first-degree relative with cancer. Twelve mutations of unknown significance were also identified. An association was also noted between the presence of common polymorphisms in BRCA1 and family history of cancer. Polymorphisms were present at higher frequency among women without a family history of cancer compared to women with positive family histories, suggesting they are associated with reduced risk.
In a clinic-based series of ovarian cancer patients, germline BRCA1 mutations were detected in 12 of 258 (4.6%) patients. A strong correlation was noted between the presence of mutations and family history of breast and/or ovarian cancer, indicating that these women are most likely to benefit from genetic susceptibility testing.
本研究旨在确定在一组未经选择的、基于临床的卵巢癌病例中BRCA1基因改变的频率；评估家族史在预测致病突变可能性方面的作用；记录BRCA1基因多态性变异的发生情况，并根据乳腺癌和/或卵巢癌病史确定其在家族中的分布。
对258例原发性上皮性卵巢癌女性患者进行分析，这些患者参与了妇科肿瘤学组的一项非临床方案，通过单链构象多态性分析检测BRCA1基因种系改变。
在12例患者（4.6%）中鉴定出BRCA1基因的蛋白质截短突变。BRCA1突变携带者的癌症诊断中位年龄为47岁，而未发生突变的患者为57岁（P = 0.02）。除1例患者外，所有BRCA1突变患者均报告有乳腺癌和/或卵巢癌家族史，其中8例有一级亲属患癌。还鉴定出12个意义不明的突变。BRCA1基因常见多态性的存在与癌症家族史之间也存在关联。与有阳性家族史的女性相比，无癌症家族史的女性中多态性出现的频率更高，表明它们与降低的风险相关。
在一组基于临床的卵巢癌患者中，258例患者中有12例（4.6%）检测到种系BRCA1突变。突变的存在与乳腺癌和/或卵巢癌家族史之间存在强烈相关性，表明这些女性最有可能从遗传易感性检测中获益。
